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Stem Cell Reports. 2016 Jul 12;7(1):1-10. doi: 10.1016/j.stemcr.2016.05.012. Epub 2016 Jun 23.

MiR-31/SDHA Axis Regulates Reprogramming Efficiency through Mitochondrial Metabolism.

Author information

1
Department of Microbiology and Immunology, Indiana University School of Medicine, 950 West Walnut Street, Indianapolis, IN 46202-5181, USA; Soonchunhyang Institute of Medi-bio Science, Institute of Tissue Regeneration, Soon Chun Hyang University, Asan-si, 31151 Chungcheongnam-do, Republic of Korea. Electronic address: leeman@sch.ac.kr.
2
Department of Microbiology and Immunology, Indiana University School of Medicine, 950 West Walnut Street, Indianapolis, IN 46202-5181, USA.
3
Soonchunhyang Institute of Medi-bio Science, Institute of Tissue Regeneration, Soon Chun Hyang University, Asan-si, 31151 Chungcheongnam-do, Republic of Korea.
4
School of Medicine, Kon Kuk University, 05029 Seoul, Republic of Korea.
5
Department of Microbiology and Immunology, Indiana University School of Medicine, 950 West Walnut Street, Indianapolis, IN 46202-5181, USA. Electronic address: hbroxmey@iupui.edu.

Abstract

Metabolism is remodeled when somatic cells are reprogrammed into induced pluripotent stem cells (iPSCs), but the majority of iPSCs are not fully reprogrammed. In a shift essential for reprogramming, iPSCs use less mitochondrial respiration but increased anaerobic glycolysis for bioenergetics. We found that microRNA 31 (miR-31) suppressed succinate dehydrogenase complex subunit A (SDHA) expression, vital for mitochondrial electron transport chain (ETC) complex II. MiR-31 overexpression in partially reprogrammed iPSCs lowered SDHA expression levels and oxygen consumption rates to that of fully reprogrammed iPSCs, but did not increase the proportion of fully reprogrammed TRA1-60(+) cells in colonies unless miR-31 was co-transduced with Yamanaka factors, which resulted in a 2.7-fold increase in full reprogramming. Thus switching from mitochondrial respiration to glycolytic metabolism through regulation of the miR-31/SDHA axis is critical for lowering the reprogramming threshold. This is supportive of multi-stage reprogramming whereby metabolic remodeling is fundamental.

PMID:
27346679
PMCID:
PMC4944586
DOI:
10.1016/j.stemcr.2016.05.012
[Indexed for MEDLINE]
Free PMC Article

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